Computational modeling and numerical methods for spatiotemporal calcium cycling in ventricular myocytes

• Main Authors: Michael eNivala, Enno ede Lange, Robert eRovetti, Zhilin eQu
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2012-05-01
• Series: Frontiers in Physiology
• Subjects: mathematical modeling; calcium cycling; graphical processing unit computing; ventricular myocyte
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00114/full

Intracellular calcium (Ca) cycling dynamics in cardiac myocytes is regulated by a complex network of spatially distributed organelles, such as sarcoplasmic reticulum (SR), mitochondria, and myofibrils. In this study, we present a mathematical model of intracellular Ca cycling and numerical and computational methods for computer simulations. The model consists of a coupled Ca release unit (CRU) network, which includes a SR domain and a myoplasm domain. Each CRU contains 10 L-type Ca channels and 100 ryanodine receptor channels, with individual channels simulated stochastically using a varient of Gillespie’s method, modified here to handle time-dependent transition rates. Both the SR domain and the myoplasm domain in each CRU are modeled by 5x5x5 voxels to maintain proper Ca diffusion. Advanced numerical algorithms implemented on graphical processing units were used for fast computational simulations. For a myocyte containing 100x20x10 CRUs, a one-second heart time simulation takes about 10 minutes of machine time on a single NVIDIA Tesla C2050. Examples of simulated Ca cycling dynamics, such as Ca sparks, Ca waves, and Ca alternans, are shown.